In a 10-year microsimulation model, baxdrostat was projected to reduce cardiovascular deaths by 5.8% (absolute reduction 4.5 per 1,000 patients) compared with spironolactone.
Does baxdrostat reduce clinical events and mortality compared to spironolactone in patients with resistant hypertension?
A microsimulation model suggests that baxdrostat may meaningfully reduce fatal and non-fatal cardiovascular events over 10 years compared to spironolactone in patients with resistant hypertension.
Absolute Risk Reduction: 0.45
Absolute Event Rate: 7.42% vs 7.87%
Absolute Risk Reduction: 0.45%
Objective: Resistant hypertension (rHTN) remains a major clinical challenge. Spironolactone, despite non-selective MR antagonism contributing to potential for off-target side effects, is used for the treatment of rHTN. Baxdrostat, a selective aldosterone synthase inhibitor, safely reduces 24-hour blood pressure in rHTN. We employed a hypertension model to assess the potential clinical impact of baxdrostat versus spironolactone. Design and method: The baxdrostat hypertension model (BAX-HTN), a patient-level Monte Carlo microsimulation model, was developed. Baseline rHTN patient demographics and comorbidities were derived from Clinical Practice Research Datalink (CPRD) data, informing baseline clinical events and mortality risks using published risk equations. Risks were modified by treatment impact on office blood pressure OBPM, 24-hour ambulatory blood pressure ABPM, and urinary albumin–creatinine ratio uACR. Blood pressure (BP) reductions were derived using a network meta-analysis of baxdrostat versus spironolactone using published data (baxdrostat: δ ABPM -14.17 mmHg and δ OBPM -10.19 mmHg; spironolactone: δ ABPM -6.63 mmHg and δ OBPM -9.93 mmHg). Treatment durations were informed by published literature, real-world evidence, and clinical expert opinion. The model dynamically updated BP, uACR, comorbidities and subsequent treatments. Outcomes included clinical events and mortality over a 10-year time horizon. Results: Over 10-years, the BAX-HTN model predicted 78.7 cardiovascular deaths and 427.6 non-cardiovascular deaths per 1,000 patients with rHTN receiving spironolactone. Baxdrostat was projected to have a relative risk reduction of 5.8% and 5.9% for cardiovascular and non-cardiovascular deaths, respectively (projected absolute risk reduction: 4.5 cardiovascular deaths and 24.4 non-cardiovascular death per 1,000 patients). Compared with spironolactone, baxdrostat was projected to reduce the incidence of non-fatal cardiovascular events, including myocardial infarction (4.0%), unstable angina (3.6%), stroke (9.7%), transient ischemic attack (9.6%) and heart failure (4.4%). Conclusions: Patients with rHTN receiving spironolactone continue to face substantial long term risk. Incorporating baxdrostat into the treatment pathway may meaningfully reduce both fatal and non fatal clinical events over a 10 year horizon. These findings highlight a significant unmet clinical need in rHTN and support the potential value of baxdrostat as an alternative therapeutic option.
Jhund et al. (Fri,) conducted a other in Resistant hypertension. Baxdrostat vs. Spironolactone was evaluated on Cardiovascular deaths over 10 years (RRR 5.8%). In a 10-year microsimulation model, baxdrostat was projected to reduce cardiovascular deaths by 5.8% (absolute reduction 4.5 per 1,000 patients) compared with spironolactone.